We have defined propagable, quantifiable differences between normal and rheumatoid synovial cells in tissue culture. These differences are due, at least in part, to Connective Tissue Activating Peptide/s (CTAP/s) present in excess in rheumatoid cells. CTAP/s are small basic peptides which stimulate glycosaminoglycan synthesis, sulfate incorporation into proteoglycans, glycolysis and DNA synthesis in cell culture. CTAP-I (of lymphocyte origin) stimulates glycolysis and hyaluronic acid synthesis while CTAP-III (of platelet origin) has the additional ability to stimulate DNA formation by human synovial, cartilage, thyroid and skin fibroblasts in cell culture. These actions of CTAP/s, and their widespread cellular distribution, qualify these mediators for a role as key regulators of inflammation, modifying progression from the exudative to the reparative phase. Measurements of CTAP/s in simple inflammation show an early peak of activity, and continued excess of CTAP/s was shown to produce the biochemical activities characteristic of chronic rheumatoid inflammation. The major goals of the proposal are: 1. To identify peptide mediators (CTAP/s) of connective tissue metabolism in relevant human tissues, cells and body fluids. 2. To isolate selected CTAP/s and characterize their chemical properties. 3. To better define the connective tissue activation process.